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Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies.
Biol Blood Marrow Transplant. 2007 Feb; 13(2):235-44.BB

Abstract

Results of allogeneic hematopoietic stem cell transplantation (HCT) to treat advanced leukemia or myelodysplastic syndrome (MDS) remain poor due to excessive relapse and transplant-related mortality. To improve transplant outcome in this patient population, 43 patients (median age, 46.1 years) with high-risk or advanced lymphoid (n = 5) or myeloid malignancy (n = 38) were prospectively enrolled on a pilot trial of cytoreduction with intravenous busulfan and melphalan followed by an unmodified HLA-A, -B, and -DRbeta1-matched related (n = 18) or unrelated (n = 25) HCT. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-four patients had > or = 5% blasts at the time of HCT; 12 of these had > 20% blasts. Seventeen patients had unfavorable cytogenetics, 8 patients underwent transplantation for secondary MDS or acute myelogenous leukemia, and 4 patients had relapsed after a previous allogeneic transplantation. Although mucositis was the most significant regimen-related toxicity, requiring the addition of folinic acid rescue and failure to receive all 4 doses of methotrexate in 23 patients, the nonrelapse mortality at 30 and 100 days was low at 0% and 16%, respectively. The cumulative incidence of grade II-IV acute GVHD was 24%, and that of extensive chronic GVHD was 7%. With a minimum follow-up of 18 months, the estimated 3-year overall survival is 37% and the estimated disease-free survival (DFS) is 33%. For 18 patients with MDS (< or = RAEB-2) or high-risk myeloproliferative disorder, the estimated 3 year DFS is 61%. These data demonstrate the curative potential of this regimen in patients with high-risk myeloid malignancies.

Authors+Show Affiliations

Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. smallt@mskcc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

17241929

Citation

Small, Trudy N., et al. "Intravenous Busulfan and Melphalan, Tacrolimus, and Short-course Methotrexate Followed By Unmodified HLA-matched Related or Unrelated Hematopoietic Stem Cell Transplantation for the Treatment of Advanced Hematologic Malignancies." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 13, no. 2, 2007, pp. 235-44.
Small TN, Young JW, Castro-Malaspina H, et al. Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies. Biol Blood Marrow Transplant. 2007;13(2):235-44.
Small, T. N., Young, J. W., Castro-Malaspina, H., Prockop, S., Wilton, A., Heller, G., Boulad, F., Chiu, M., Hsu, K., Jakubowski, A., Kernan, N. A., Perales, M. A., O'Reilly, R. J., & Papadopoulos, E. B. (2007). Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 13(2), 235-44.
Small TN, et al. Intravenous Busulfan and Melphalan, Tacrolimus, and Short-course Methotrexate Followed By Unmodified HLA-matched Related or Unrelated Hematopoietic Stem Cell Transplantation for the Treatment of Advanced Hematologic Malignancies. Biol Blood Marrow Transplant. 2007;13(2):235-44. PubMed PMID: 17241929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies. AU - Small,Trudy N, AU - Young,James W, AU - Castro-Malaspina,Hugo, AU - Prockop,Susan, AU - Wilton,Andrew, AU - Heller,Glenn, AU - Boulad,Farid, AU - Chiu,Michelle, AU - Hsu,Katherine, AU - Jakubowski,Ann, AU - Kernan,Nancy A, AU - Perales,Miguel-Angel, AU - O'Reilly,Richard J, AU - Papadopoulos,Esperanza B, PY - 2006/09/05/received PY - 2006/10/10/accepted PY - 2007/1/24/pubmed PY - 2007/3/14/medline PY - 2007/1/24/entrez SP - 235 EP - 44 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 13 IS - 2 N2 - Results of allogeneic hematopoietic stem cell transplantation (HCT) to treat advanced leukemia or myelodysplastic syndrome (MDS) remain poor due to excessive relapse and transplant-related mortality. To improve transplant outcome in this patient population, 43 patients (median age, 46.1 years) with high-risk or advanced lymphoid (n = 5) or myeloid malignancy (n = 38) were prospectively enrolled on a pilot trial of cytoreduction with intravenous busulfan and melphalan followed by an unmodified HLA-A, -B, and -DRbeta1-matched related (n = 18) or unrelated (n = 25) HCT. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-four patients had > or = 5% blasts at the time of HCT; 12 of these had > 20% blasts. Seventeen patients had unfavorable cytogenetics, 8 patients underwent transplantation for secondary MDS or acute myelogenous leukemia, and 4 patients had relapsed after a previous allogeneic transplantation. Although mucositis was the most significant regimen-related toxicity, requiring the addition of folinic acid rescue and failure to receive all 4 doses of methotrexate in 23 patients, the nonrelapse mortality at 30 and 100 days was low at 0% and 16%, respectively. The cumulative incidence of grade II-IV acute GVHD was 24%, and that of extensive chronic GVHD was 7%. With a minimum follow-up of 18 months, the estimated 3-year overall survival is 37% and the estimated disease-free survival (DFS) is 33%. For 18 patients with MDS (< or = RAEB-2) or high-risk myeloproliferative disorder, the estimated 3 year DFS is 61%. These data demonstrate the curative potential of this regimen in patients with high-risk myeloid malignancies. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/17241929/Intravenous_busulfan_and_melphalan_tacrolimus_and_short_course_methotrexate_followed_by_unmodified_HLA_matched_related_or_unrelated_hematopoietic_stem_cell_transplantation_for_the_treatment_of_advanced_hematologic_malignancies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(06)00677-X DB - PRIME DP - Unbound Medicine ER -